Photomicrographs from sections of the anterior scleral tumor. A, The spindle cell tumor had a myxoid background with nuclei that are curved and tapered at the ends (hematoxylin-eosin, original magnification ×250). Inset, The drawing shows the size and distribution of the 6 episcleral nerve sheath tumors. The numbers refer to the percentage of Axenfeld nerve loops at the various positions as noted by Stevenson.9 B, Marked reactivity for S100 protein antibody in most of the cells (original magnification ×100). C, Antineurofilament antibody reacts with occasional axonal fibers in the tumor (original magnification ×400). D, An overview of the lesion shows fibrous tissue at the base but a lack of defined encapsulation (hematoxylin-eosin, original magnification ×20). Inset, Trichrome stain shows the infiltrative edge of the lesion (original magnification ×100).

The occurrence of solitary episcleral neurofibroma has been described previously in 3 case reports1- 4; episcleral schwannomas have been reported 4 times.5- 8 The origin of these rare tumors is unknown. However, topographic analysis from our case and those in the literature provides evidence that most anterior scleral nerve sheath tumors arise from intrascleral nerve loops.

Report of Cases

A 45-year-old woman had a mildly tender, white nodule of a few weeks' duration that was adherent to the sclera, measuring 3.5 × 3.5 mm in surface dimension and located approximately 4 mm from the limbus in the inferotemporal quadrant. Neither prior eye operations nor traumatic injury occurred in this region. Microscopic examination of histologic sections revealed a spindle cell tumor with features of a nerve sheath tumor (Figure). The tumor did appear encapsulated.

Cases culled from the literature of episcleral nerve sheath tumors are summarized in the Table. Under the assumption that benign nerve sheath tumors enlarge in a symmetric fashion, the distance of the tumor from the limbus (d) was calculated from the photograph by the following equation: d = (dphotograph)(11.7)/c, where c indicates the mean corneal diameter in millimeters measured in the photograph and 11.7 represents the corneal diameter in millimeters.10

The key characteristics of episcleral peripheral nerve sheath tumors are shown in the Table. The mean age of the patients was 39.5 years. The mean distance from the limbus to the center of the tumor for anterior neurofibroma and schwannoma was 4 mm. The relative size and topographic location of the lesions are shown in the inset of part A of the Figure.

Comment

Episcleral neurofibromas and schwannomas likely arise from the long posterior ciliary nerves within the sclera.3 The ciliary nerves pierce the sclera near the optic nerve and pass anteriorly within the sclera and suprachoroidal space while branching to form a loose connection between the long and short posterior ciliary nerves, leading to 20 to 30 branches at the level of the ciliary body.11,12 The nerve loop of Axenfeld is an anastomotic interconnection of the long ciliary nerve that occasionally turns to enter the sclera before turning back again to continue anteriorly to the ciliary body.13 The loops occur in the area 2 to 4 mm posterior to the limbus, and no loops occur in the zones directly anterior to the medial and lateral rectus tendons.9

Anterior episcleral nerve sheath tumors have a topographic distribution similar to the Axenfeld nerve loop, permitting speculation of their relationship. The distances from the center of the tumor to the limbus narrowly ranged from 3 to 4 mm. None of these tumors occurred directly anterior to the horizontal rectus muscle tendons (Table). The anterior tumors were evenly distributed among the remaining quadrants as described for Axenfeld nerve loops. Two of 4 episcleral schwannomas occurred in the posterior sclera. If the distribution were random in the ciliary nerves, then some tumors would be expected to be found in the horizontal plane and at more variable distances from the limbus.

The apex of the loop can extend through the full thickness of the sclera and project above the scleral surface.13 Pain and tenderness have been noted when the nerve loops are located anteriorly. The sharp bend in the nerve and the ensuing stress perhaps facilitate the abnormal proliferation of nerve sheath cells and the formation of these tumors. The differential diagnosis for all of the reported episcleral nerve sheath tumors includes solitary circumscribed neuroma, but as in our case the published cases lack sufficient encapsulation to warrant this diagnosis.